Titanocene(III) mediated radical cyclizations of epoxides for the synthesis of medium-sized cyclic ethers

Titanocene(III) chloride (Cp₂TiCl) mediated 7-exo and 8-endo radical cyclizations of epoxides towards the synthesis of 7- and 8-membered cyclic ethers have been described. Titanocene(III) chloride was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and activated zinc dust in THF.     

Titanocene(III) mediated 8-endo radical cyclizations for the synthesis of eight-membered cyclic ethers

Titanocene(III) chloride (Cp₂TiCl) mediated 8-endo radical cyclizations towards the synthesis of eight-membered cyclic ethers have been described. Titanocene(III) chloride was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and activated zinc dust in THF.     

Titanocene (III) chloride mediated radical induced synthesis of (−)-methylenolactocin and (−)-protolichesterinic acid

Enantioselective synthesis of two anti-tumor antibiotics, (−)-methylenolactocin and (−)-protolichesterinic acid, has been achieved through titanocene(III) chloride mediated radical cyclization reaction starting from commercially available d-mannitol. Titanocene(III) chloride (Cp₂TiCl) was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and zinc dust in THF.     

Titanocene(III) chloride mediated radical induced asymmetric synthesis of α-methylene bis-γ-butyrolactone

Asymmetric synthesis of α-methylene bis-γ-butyrolactone has been synthesized using titanocene(III) chloride as a radical source. Titanocene(III) chloride (Cp₂TiCl) was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and zinc dust in THF.     

Similarities and differences of epoxide, aldehyde and peroxide initiators for Cp2TiCl-catalyzed styrene living radical polymerizations

Cp₂TiCl is the first example of a single electron transfer (SET) agent that both provides initiating radicals from three different types of functionalities (i.e. radical ring opening of epoxides and reduction of aldehydes and peroxides) and doubles as mediator for the living radical polymerization of styrene (St) by reversibly endcapping the growing polymer chains. An initiator (I) comparison was performed using 1,4-butanediol diglycidyl ether (BDE), benzaldehyde (BA) and benzoyl peroxide (BPO) as models. The investigation of the effect of reaction variables was carried out over a wide range of experimental conditions ([Cp₂TiCl₂]/[I] = 0.5/1-4/1; [Zn]/[Cp₂TiCl₂] = 0.5/1-3/1, [St]/[I] = 50/1-400/1 and T = 60-130 °C) to reveal living polymerization features such as a linear dependence of molecular weight on conversion and narrow molecular weight distribution (M_w/M_n) for each initiator class. However, progressively lower polydispersities and larger initiator efficiencies are obtained with increasing the [Cp₂TiCl₂]/[I] and [Zn]/[Cp₂TiCl₂] ratios and with decreasing temperature. Accordingly, optimum conditions correspond to [St]/[I]/[Cp₂TiCl₂]/[Zn] = [50-200]/[1]/[2-3]/[4-6] at 70-90 °C. By contrast to peroxides, aldehydes and the more reactive epoxides provide alcohol end groups useful in block or graft copolymers synthesis.     

Biphasic ethylene polymerisation using 1-n-alkyl-3-methylimidazolium tetrachloroaluminate ionic liquid as a medium of the Cp2TiCl2 titanocene catalyst

A systematic analysis was performed on a series of 1-n-alkyl-3-methylimidazolium tetrachloroaluminates (where alkyl = ethyl, butyl, hexyl, and octyl), applied as a medium of the Cp₂TiCl₂ titanocene catalyst, to evaluate the influence of the physical properties of the ionic liquids on the polymerisation reaction carried out in the biphasic ionic liquid/hexane mode. Two alkylaluminium compounds, AlEtCl₂ and AlEt₂Cl, were used as activators. The influence of the activator/catalyst molar ratio on the performance of the ethylene polymerisation was determined for each ionic liquid studied. The best results were obtained using 1-n-octyl-3-methylimidazolium tetrachloroaluminate. For the titanocene catalyst immobilised in the ionic liquid, AlEtCl₂ turned out to be a better activator than AlEt₂Cl in our studies. The properties of the polyethylene product have also been presented.     

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and heteroaryl-substituted titanocene anti-cancer drugs

From the carbolithiation of N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl₄ resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC₅₀ values obtained were of 240, and 28 μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene 5c with an IC₅₀ value of 5.5 μM is found to be almost as cytotoxic as cis-platin, which showed an IC₅₀ value of 3.3 μM, when tested on the LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.     

Cp2TiCl-catalyzed radical chemistry: living styrene polymerizations from epoxides, aldehydes, halides, and peroxides

Four different Cp₂TiCl-activated radical sources (1,4-butanediol diglycidyl ether, benzaldehyde, (1-bromoethyl)benzene, and benzoyl peroxide) were investigated as initiators in the Cp₂TiCl-catalyzed living radical polymerization of styrene (St). The effect of reaction variables was investigated over a wide range of values ([St]/[I]=50/1-400/1, [I]/[Cp₂TiCl₂]=1/0.5-1/4, [Cp₂TiCl₂]/[Zn]=1/0.5-1/3 and T=40-130 °C). A linear dependence of molecular weight on conversion was observed for each initiator, but larger initiator efficiencies and lower polydispersities were obtained upon increasing [Cp₂TiCl₂] and [Zn] and decreasing temperature. The optimum conditions are initiator dependent but broadly correspond to [St]/[I]/[Cp₂TiCl₂]/[Zn]=[50-200]/[1]/[2-3]/[4-6] at 70-90 °C. The most robust initiators are aldehydes followed by peroxides, epoxides, and finally halides.     

On the reversibility of the first electron transfer involving titanocene dichloride

The 1e reduction of titanocene dichloride (Cp₂TiCl₂) in DMF has been examined in detail. The reaction is reversible, in contradiction of a recent report.     

Formation of conjugated dienes by the reaction of titanocene alkenylidene complexes with alkynes

Titanocene alkenylidene complexes, generated by the reductive metallation of 1,1-dichloro-1-alkenes with the titanocene(II) species Cp₂Ti[P(OEt)₃]₂, reacted with alkynes to produce conjugated dienes.     

Studies on titanium organic compounds: VIII. Mechanism of vinyl polymerization in the presence of titanocene dichloride

The mechanism of catalytic polymerization of acrylonitrile in the presence of titanocene dichloride under light have been investigated by UV, NMR and ESR spectroscopy. Results of photochemical reaction monitored by UV and NMR showed that titanocene dichloride (Cp₂TiCl₂) in dimethyl sulfoxide system can be decomposed by light irradiation to give cyclopentadiene. ESR studies show that cyclopentadienyl free radical in photopolymerization system of Cp₂TiCl₂-acrylonitrile can be trapped by two kinds of spin trapping agents, phenyl-N-tert-butylnitrone and 2-methyl-2-nitrosopropane, respectively. Therefore, the radical mechanism of catalytic polymerization of acrylonitrile in the presence of Cp₂TiCl₂ under light is further confirmed.     

Radical promoted cyclizations of aromatic carbonyl compounds to benzopyrans using titanocene(III) chloride

Aromatic carbonyl compounds undergo smooth intramolecular radical cyclization with alkenes or alkynes using titanocene(III) chloride to furnish the corresponding benzopyrans. The radical initiator, Cp₂TiCl, was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and zinc dust in THF under argon.     

Radical-mediated synthesis of 3,4-dihydroisocoumarins: total synthesis of hydrangenol

A radically promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp₂TiCl) as the radical initiator. The total synthesis of (±)-hydrangenol has been completed using this radical technology. Cp₂TiCl was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and Zn-dust in THF under argon.     

Titanocene(III) chloride mediated radical-induced synthesis of 3,4-dihydroisocoumarins: synthesis of (±)-hydrangenol, (±)-phyllodulcin, (±)-macrophyllol and (±)-thunberginol G

A radical-promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp₂TiCl) as the radical initiator. The total synthesis of four naturally occurring dihydrocoumarins hydrangenol, phyllodulcin, macrophyllol and thunberginol G has been accomplished using the radical technology. Cp₂TiCl was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and Zn-dust in THF under argon.     

Single-step synthesis of TiC mesocrystals on the MWCNTs surface by the pyrolysis of Cp2TiCl2

Titanium carbide mesocrystals have been manufactured by the one-stage metalorganic chemical vapor deposition (MOCVD) technology using the pyrolysis of titanocene dichloride, Cp₂TiCl₂ (Cp = η⁵-C₅H₅) on the surfaces of multi-walled carbon nanotubes (MWCNTs). The initial stages of the Cp₂TiCl₂ gas-phase dissociation were modeled with density functional theory (DFT) calculations. A series of syntheses were carried out with a step-by-step increase of the Cp₂TiCl₂ amount. These experiments allows to observe intermediate stages of self-assembly of TiC mesocrystals. Thus, it was possible to identify that the decomposition of Cp₂TiCl₂ at 900 °C leads to the formation of TiC crystals nanoparticles with their accompanying self-assembly. As a final stage of this process, perfect mesocrystals of a cubic habit with a size of approximately 50 μm were found. The usage of powdered MWCNTs as a substrate in the chemical vapor deposition (CVD) processes provides heterogeneous conditions, which can be promising for the search for new forms of nanostructured materials.     

Free radical-promoted conjugate addition of activated bromo compounds using titanocene(III) chloride as the radical initiator

Free radical-promoted conjugate addition of activated bromo compounds to α,β-unsaturated ketones and reactive α,β-unsaturated esters has been described using titanocene(III) chloride (Cp₂TiCl) as the radical initiator. Cp₂TiCl was prepared in situ from commercially available Cp₂TiCl₂ and activated zinc dust in THF.     

Synthesis and structure of isopropyldimethylsilyl-substituted octamethyltitanocene

Reduction of isopropyldimethylsilyl-substituted titanocene dichloride [TiCl₂(η⁵-C₅Me₄SiMe₂Prⁱ)₂] (1) by excess magnesium in the presence of excess bis(trimethylsilyl)ethyne (btmse) in tetrahydrofuran at 60 °C yielded a mixture of products amongst them only the trinuclear Ti-Mg-Ti hydrido-bridged complex Mg[Ti(μ-H)₂(η⁵-C₅Me₄SiMe₂Prⁱ)]₂ (3) was isolated and characterized. The precursor of titanocene, [Ti(η⁵-C₅Me₄SiMe₂Prⁱ)₂(η²-btmse)] (6), was obtained from the identical system which, after initial formation of [TiCl(η⁵-C₅Me₄SiMe₂Prⁱ)₂] (2), reacted at −18 °C overnight and then the solution was rapidly separated from the remaining magnesium. Titanocene [Ti(η⁵-C₅Me₄SiMe₂Prⁱ)₂] (7) was obtained by thermolysis of 6 at 75 °C in vacuum. Crystal structures of 1, 2, 3, 6, and 7 were determined.     

Syntheses, structures, and properties of phenyltrihydroborate complexes of zirconocene and titanocene

The phenyltrihydroborate complexes, Cp₂ZrCl{(μ-H)₂BHPh}, 1, and Cp₂Zr{(μ-H)₂BHPh}₂ · (1/2 toluene), 2, were prepared from the reactions of Cp₂ZrCl₂ with one and two moles of LiBH₃Ph. The Zr-H-B bonds in 2 are stable under vacuum at 100 °C for hours without significant decomposition. An inductive effect has been proposed for this strong interaction. This hydrogen bridge bond can be broken upon reacting with the Lewis base N(C₂H₅)₃ to produce (C₂H₅)₃N · BH₂Ph and the zirconium hydride compound Cp₂ZrH{(μ-H)₂BHPh}, 3. Compound 3 also can be prepared from the reaction of Cp₂ZrHCl with LiBH₃Ph. The reaction of 1 with the Lewis acid B(C₆F₅)₃ is solvent dependent, the metathesis product Cp₂ZrCl{(μ-H)₂B(C₆F₅)₂}, 4, was formed in the toluene solution, whereas the ionic complex [Cp₂ZrCl(OEt₂)][HB(C₆F₅)₃], 5, was isolated from the ether solution. The reaction of titanocene dichloride, Cp₂TiCl₂, with LiBH₃Ph produced a 17-electron, paramagnetic complex, Cp₂Ti{(μ-H)₂BHPh}, 6. Single crystal X-ray structures of 1, 2, 3, 4, 5, and 6 were also determined. A coplanar structure of the four bridge hydrogens in 2 was observed.     

Reactivity of the unsaturated dimolybdenum anion [Mo2(η-C5H5)2(μ-PCy2)(μ-CO)2] towards electrophiles based on p- and d-block elements

The 30-electron binuclear anion [Mo₂Cp₂(μ-PCy₂)(μ-CO)₂]⁻ reacts with the chlorophosphite ClP(OEt)₂ or the organotin chlorides Cl₂SnPh₂ or ClSnPh₃ to give compounds of the formula trans-[Mo₂Cp₂(μ-E)(μ-PCy₂)(CO)₂], (E = P(OEt)₂, SnPh₃, SnPh₂Cl). In contrast, this anion reacts with the organosilicon chlorides ClSiR₃ (R = Ph, Me) to give unstable silyloxycarbyne-bridged complexes [Mo₂Cp₂(μ-PCy₂)(μ-COSiR₃)(μ-CO)], which rapidly hydrolyze to give the known hydride [Mo₂Cp₂(μ-H)(μ-PCy₂)(CO)₂]. Two main types of products were also observed in the reactions of the title anion with different chlorocomplexes of the transition and post-transition metals. Thus, the reactions with [MCl₂Cp₂] (M = Ti, Zr) give moisture-sensitive isocarbonyl-bridged complexes of the type [Mo₂Cp₂(μ-COMClCp₂)(μ-PCy₂)(μ-CO)]. In contrast, softer metallic electrophiles such as [AuCl(PR₃)] (R = ⁱPr, ptol) react with the anion at the dimolybdenum site to form new trimetallic clusters of the formula [AuMo₂Cp₂(μ-PCy₂)(CO)₂(PR₃)], also retaining a Mo−Mo triple bond. Subsequent reactions of the latter products with the solvate complexes [Au(PR₃)(THF)][PF₆] give the tetranuclear clusters [Au₂Mo₂Cp₂(μ-PCy₂)(CO)₂(PR₃)₂][PF₆] (Mo−Mo = 2.5674(3) Å and Au−Au = 2.7832(2) Å when R = ⁱPr). Finally, the reaction of the title anion with HgI₂ gives the pentanuclear cluster [Hg{Mo₂Cp₂(μ-PCy₂)(CO)₂}₂] or the trinuclear cluster [Mo₂Cp₂(μ-HgI)(μ-PCy₂)(CO)₂] depending on the stoichiometry being actually used for the reaction. The trinuclear species is only stable in tetrahydrofuran (THF), and decomposes to give a mixture of the dimeric species [Mo₂Cp₂(μ-HgI)(μ-PCy₂)(CO)₂]₂ along with variable amounts of the known iodide-bridged complex [Mo₂Cp₂(μ-I)(μ-PCy₂)(CO)₂].     

Ethylene polymerization by novel 4,4′-bis(methylene)biphenylene bridged homodinuclear titanocene and zirconocene combined with MAO

4,4′-Bis(methylene)biphenylene bridged homodinuclear titanocene (3) and zirconocene (4) have been synthesized by treatment of CpTiCl₃ and CpZrCl₃ · DME with Na₂[C₅H₄CH₂C₆H₄-p-C₆H₄CH₂C₅H₄], respectively, in THF and characterized by ¹H NMR and element analysis. After activation with methyl aluminoxane (MAO), these catalysts were used for the homogeneous polymerization of ethylene. The influences of reaction conditions, such as temperature, time, catalyst concentration and molar ratio of MAO/Cat. on ethylene polymerization were investigated in detail. The catalytic activities of 3 and 4 are more than three times higher than that of the phenyldimethylene bridged homodinuclear metallocene of titanocene (5) and zirconocene (6), respectively, and also twice higher than that of Cp₂TiCl₂/MAO and Cp₂ZrCl₂/MAO, respectively. However, the catalytic activity of 3 is nearly half as high as that of 4, which reached 1.31 × 10⁶ g PE/mol cat h. The molecular weight of polyethylene increases simultaneously with prolongation of polymerization time. GPC spectra show that 3 and 4 produce polyethylene with broad molecular weight distribution (4.28 and 3.18). The high melting points of the products (131-134 °C) indicate that the polyethylene formed is highly linear and highly crystalline.